Genetic Variant CEBPB:p.Asp124Glu (chr20-50191405-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005194.4(CEBPB):c.372C>A(p.Asp124Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,517,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CEBPB
NM_005194.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.988

Publications

1 publications found

Variant links:

Genes affected

CEBPB (HGNC:1834): (CCAAT enhancer binding protein beta) This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain. The encoded protein functions as a homodimer but can also form heterodimers with CCAAT/enhancer-binding proteins alpha, delta, and gamma. Activity of this protein is important in the regulation of genes involved in immune and inflammatory responses, among other processes. The use of alternative in-frame AUG start codons results in multiple protein isoforms, each with distinct biological functions. [provided by RefSeq, Oct 2013]

CEBPB links:

CEBPB-AS1 (HGNC:51226): (CEBPB antisense RNA 1)

CEBPB-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043746352).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEBPB	NM_005194.4	MANE Select	c.372C>A	p.Asp124Glu	missense	Exon 1 of 1	NP_005185.2
CEBPB	NM_001285878.1		c.303C>A	p.Asp101Glu	missense	Exon 1 of 1	NP_001272807.1	P17676-2
CEBPB	NM_001285879.1		c.-223C>A		5_prime_UTR	Exon 1 of 1	NP_001272808.1	P17676-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEBPB	ENST00000303004.5	TSL:6 MANE Select	c.372C>A	p.Asp124Glu	missense	Exon 1 of 1	ENSP00000305422.3	P17676-1
CEBPB	ENST00000718336.1		c.372C>A	p.Asp124Glu	missense	Exon 1 of 1	ENSP00000520773.1	P17676-1
CEBPB-AS1	ENST00000613921.1	TSL:3	n.94G>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000683

AC:

AN:

146404

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1366584

Hom.:

Cov.:

AF XY:

0.00000886

AC XY:

AN XY:

677158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27794

American (AMR)

AF:

0.00

AC:

AN:

35342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23250

East Asian (EAS)

AF:

0.00

AC:

AN:

30384

South Asian (SAS)

AF:

0.00

AC:

AN:

78536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

1062488

Other (OTH)

AF:

0.0000180

AC:

AN:

55416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150678

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73526

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67458

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000869

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.13

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

0.99

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.070

REVEL

Benign

0.016

Sift

Benign

0.75

Sift4G

Benign

1.0

Polyphen

0.010

Vest4

0.059

MutPred

0.19

Loss of stability (P = 0.054)

MVP

0.15

MPC

1.3

ClinPred

0.018

GERP RS

2.2

Varity_R

0.049

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over